Download PowerPoint ****

Pathophysiology
Department of Pathophysiology
Shanghai Jiao-Tong University School of Medicine
Chapter 13
Cardiac Dysfunction
Content
Introduction
Causes and Triggers of Cardiac Dysfunction
Classification of Cardiac Dysfunction
System Compensation to Cardiac Dysfunction
Mechanisms and Pathogenesis of Heart Disease
Clinical Manifestation and Patho-physiology of
Cardiac Dysfunction
Pathophysiological basis for the Prevention and
Treatment of Cardiac Dysfunction
Vagus
Nerve
Synpathatic
Nerve
–
+
Sinus-Atrial
Node
ExcitationContraction
Coupling
Atrial
Contraction
Septum
Bundle of His
Intra-ventricular
Conduction
ExcitationContraction
Coupling
Ventricular
Contraction
Definition of Heart Failure
Definition of Heart Failure
Loss of cardiac pump activity due to systolic or
diastolic dysfunction, leading to insufficient cardiac
output and mis-matched tissue perfusion to meet the
metabolic demand. The pathogenic process and the
resulting syndrome are defined as heart failure.
 Myocardial failure
 Congestive heart failure
 Cardiac dysfunction
Congestive Heart Failure (CHF)
CHF represents a late stage of chronic heart
failure. Loss of cardiac output and venous return
mismatch cause increased plasma sodium level,
systemic water retention and increased blood volume,
leading to peripheral tissue swelling and cardiac
chamber dilation as its main symptoms.
Causes of HF
I. Congenital Heart Disease
1．Defects in Cardiac Myofilament
2．Defects in Cardiac Bioenergenic
Metabolism
II. Chronic Cardiac Overload
1．Pressure overload
2．Volume Overload
III. Ventricular Insufficient Filling
Pressure Overload
Volume Overload
Blocking of Aortic Outflow：
Aortic Valve Stenosis Aortic Valve Insufficiency
Left Ventricle Aortic Stenosis Mitral Insufficiency
Asymmetric Ventricular Hypertrophy
Aneurysm
Hypertension
Pulmonary Hypertension Atrial Septal Defects
Right Ventricle Pulmonary aneurysm
Ventricle septal defects
Pulmonary artery stenosis Tricupsid Insufficiency Chronic
Pulmonary Congestion Pulmonary aortic valve insufficiency
Bi-Ventricular High Blood viscosity Arteriovenous fistula 、Anemia,
Fever, Hyperthyroidism
Triggers and Risk Factors
I. Infection
Increased cardiac load due to enhanced metabolism during fever；
Increased heart rate leading to higher oxygen consumption and reduced
coronal perfusion in diastolic phase leading to reduced blood and oxygen
supply.
Endotoxin direct injury to cardiomyocytes
Lung infection further reduces oxygen supply to heart
II. Acid/Base Imbalance and Eletrolyte Metabolism
Acidosis
① H+ binding to Tropon
② Inhibition of SR calcium Release
Hyperkalemia
III. Arrhythmia
Loss of atrial/ventricular coordination, insufficeint ventricular filling
and ejection
Reduced diastolic phase, coronary perfusion decrease and myocardial
ischemia
Tachycardia increases oxygen consumption and aggravates ischemia
IV. Pregnancy Blood volume overload
V. Others Physical and emotional stress, infusion too
much/too fast, anemia, Digitalis poisoning
Classifications of HF
Acute versus chronic heart failure
High-output versus low-output heart failure
Right-sided versus left-sided heart failure
Contractive versus diastolic heart failure
High output heart failure
The cardiac output tends to be elevated in patients with heart
failure secondary to hyperthyroidism, anemia, arteriovenous
fistulas, beriberi. Due to high metabolic demand, the mismatch
remains.
Compensatory mechanism in Heart Failure
Contractility 
HF
SV  HR = CO 
Compensation
Heart
Tissue oxygen and
blood supply
HR
Volume Force relation
Remodeling
Peripheral Blood Volume
Redistribution
Contractility 
Relaxation
CO
SV 
Effective Blood Circulation
Supply
Cardiac Blood Supply
RBC, Hemoglobin
ODC right shift
Mitochondria，ETC
Oxygen
Utilization
Heart Rate
Quick response, heart rate leading to
increased output within certain limit
Limitation
Higher HR（＞180bpm）increases oxygen consumption
Reduced diastolic phase decreases crononary flow
and impairs cardaic perfusion
Pathogenesis of Heart Failure
Myocyte depolarization
Cytosolic Ca2+increases from 10-7
至10-5mol/L
Ca2+binds to TnC，conformational change
Excitation contraction
coupling
TnI removed ，TnT triggers myosin rotation
Expose myosin activity and forming cross-bridge, Ca2+
activates myosin ATPase, hydrolysis of ATP to produce
energy
Myosin head rotation, myofilament sliding.
Contraction of heart muscle
Myofilament sliding Model
Key factors to maintain normal systolic and
diastolic function
• Thick/thin myofilament structure
• Ca2+cycling and homeostasis
• Energy supply and utilization
I. Systolic Dysfunction
1. Injured myocyte
2. Metabolic defects
3. EC coupling defects
4. Decompensate remodeling
II. Ventricular Diastolic Defects
1. Prolonged Calcium Reuptake
2. Cross-bridge Cycling
3. Diastolic Potential
4. Ventricular Compliance reduced
III. Asynchronized Relaxation
Causes and mechanism of HF in late stage
hypertrophy
• Ischemia/hypoxia due to insufficient coronary supply；
• Sympathatic stimulation and Catecholamine signaling
defects
• Myosin isoform switch from  to ，ATPase activity is
reduced
• Ion channels, receptors, ion pumps and mitochondrial
defects；
• Interstitial fibrosis and compliance defects
• Reduced volume vs. surface ratio.
• Sustained oxygen consumption。
Functional & metabolic alterations in
Heart Failure
•
Heart failure causes organ metabolic changes due to
defective cardiac pump. Three major clinical features:
•
Cardiac output reduction
•
Tissue blood supply reducdtion
•
Venous (peripheral and pulmonary)
congestion
Blood pressure change
Venous hypertension and congestion
Increased blood volume and decreased blood
flow
Remodeling in Heart
Reduced Cardiac Reserve
Parameters for Cardiac function：
CO，CI
Parameters for contractility：
EF，Vmax，+dp/dtmax
Parameters for relaxation and compliance：
–dp/dtmax，T value，ventricular filling volume，
ventricular filling rate
Parameters for end-diastolic function：
PAWP/PCWP，CVP
Pulmonary congestion
Short of Breath
Causes：Congestion, Congestion
and Edema
symptoms
short of breath after labor
Sleep apnea
orthopnea
Pulmonary edema
•Compliance
•V/Q ratio
•Cap sensor
•Bronchial
congestion and
edema
Pulmonary Edema
1、Pulmonary capillary pressure
2、pulmonary
capillary permeability
Short of Breath
Orthopnea
Mild heart failure. Symptomatic
after physical activity and return to
normal after rest
Severe heart failure, symptomatic at rest
and short of beath even laying down.
Have to take sitting position
Sleep apnea
LV failure, short of breath in sleep
leading to coughing
Short of breath after physical activities
Under physical activity, cardiac return increases, aggravate
pulmonary congestion. Pulmonary compliance reduced,
leading to higher work load of breathing.
 increased heart rate, reduced diastolic phase and LV
return is shortened, leading to more severe pulmonary
congestion.
 Peripheral ischemia and CO2 retention leading to central
stimulation and harder breathing.
Orthopnea
IN sitting straight, blood pool to lower part of
body due to gravity, reduces cardiac return and
alleviate pulmonary congestion and edema.
Diaphram is lower, increases chest cavity
volume, support lung expansion.
Reduced tissue fluid entry into blood stream
and reduced total blood volume
Systemic Congestion
Jugular Veins expansion
hepatic expansion, pain,
dysfunction
Edema
Reduced Cardiac Output
Aortic Pressure reduction
Urine volume reduction
Brain function
Lethargy and pale
Other organ defecdts
• Liver function defects
• Abnormal digestive function
Water, electrolyte, Acid/base
•
•
•
•
Water/sodium homeostasis
Hpokalemia
Hypomagnesemia
Metabolic acidosis
Treatment principles of Heart Failure
Remove causal and triggering factors
Improve relaxation
Reduce afterload and preload, increase
output
Adjust humeral regulation
Control edema and reduce blood volume
Correct homeostasis of water, electrolytes
and acid/base.
Other, heart transplant